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BMS CA209370

A Master Protocol of Phase 1/2 Studies of Nivolumab in Advanced NSCLC Using Nivolumab as Maintenance after Induction Chemotherapy or as First-line Treatment Alone or in Combination with Standard of Care Therapies

  • Physician & Study Coordinator
  • Synopsis
  • Inclusion Criteria
  • Exclusion Criteria
  • Study Coordinator

    Alyse LaLiberte, MPH
    484-503-4151 

    Alyse.LaLiberte@sluhn.org
  • Treatment Agent: Nivolumab

    Synopsis:  The purpose of this master study is to test the effectiveness (how well the drug works), safety, and tolerability of an investigational drug called nivolumab (also known as BMS-936558) alone or in combination with standard of care therapies. Nivolumab is an antibody (a type of human protein) that is being tested to see if it will allow the body’s immune system to work against tumor cells. Nivolumab (Opdivo™) has been approved by the FDA for the treatment of metastatic melanoma (a type of skin cancer) and a specific type of previously treated advanced lung cancer. In this study, nivolumab is considered an investigational drug, as it is not approved by the FDA or any other agency for the indication in this study.

    • • Histologically confirmed locally advanced or stage IV NSCLC
      • Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0-2
      • Tumor tissue sections must be available for biomarker evaluation
    • • Untreated or active/progressing Central Nervous system (CNS) metastases
      • Active, known or suspected autoimmune disease
      • Known history of testing positive for HIV or AIDS
      • Active or chronic infection of hepatitis B virus or hepatitis C

     

Syndax SNDX-275-0601

A Phase 1b/2, Open-label, Dose Escalation Study of Entinostat in Combination with Pembrolizumab in Patients with Non-small Cell Lung Cancer, with Expansion Cohorts in Patients with Non-small Cell Lung Cancer and Melanoma

  • Physician & Study Coordinator
  • Synopsis
  • Inclusion Criteria
  • Exclusion Criteria
  • Study Coordinator

    Robyn Rex, RN, OCN, CCRP
    484-503-4152

    Robyn.Rex@sluhn.org
  • Treatment Agent: Pembrolizumab and Entinostat

    Synopsis:  The purpose of this study is to find out what the best dose of entinostat is when taking both entinostat and pembrolizumab together, as well as to see if there are side effects when the two drugs are combined. This study will also look at whether the combination of these two drugs may slow the progression of cancer. It will also study whether there is something in the blood that can be measured to assess how the therapy works with the patient’s immune system and/or in being able to predict how well future patients may respond to the therapy.

  • Patients with NSCLC:

    • Has histologically- or pathologically-confirmed recurrent/metastatic NSCLC.
    • If has adenocarcinoma, required to have previously been tested for anaplastic lymphoma kinase (ALK) rearrangements and epidermal growth factor receptor (EGFR) mutations, with results available for collection in this study, and, if positive, has been treated with prior EGFR or ALK therapy.
    • Received at least 1 chemotherapeutic regimen in the advanced/metastatic setting and experienced documented, unequivocal progressive disease by either RECIST 1.1 or clinical assessment.
    • Patients with NSCLC enrolled in Cohort 1 of the Expansion Phase should not have been previously treated with a PD-1/PD-L1-blocking antibody

    Patients in Expansion Phase, Cohorts 2 and 3:

    • Previously treated with a PD-1/PD-L1-blocking antibody and experienced experienced documented, unequivocal progressive disease by irRECIST during or after such treatment.

    Patients with Melanoma:

    • Has a histologically- or cytologically-confirmed diagnosis of unresectable or metastatic melanoma and experienced unequivocal progressive disease following a PD-1 or PD-L1-blocking antibody and, if BRAF V600 mutation-positive, a BRAF inhibitor.

    All Patients :

    • Aged 18 years or older on the day written informed consent is given.
    • If has brain metastases, must have stable neurologic status following local therapy for at least 4 weeks without the use of steroids or on stable or decreasing dose of ≤10 mg daily prednisone (or equivalent), and must be without neurologic dysfunction that would confound the evaluation of neurologic and other AEs.
    • Evidence of locally recurrent or metastatic disease based on imaging studies within 28 days before the first study drug dose:
      • At least 1 measurable lesion ≥20 mm by conventional techniques or ≥10 mm by spiral CT scan or MRI, with the last imaging performed within 28 days before the first study drug dose. If there is only 1 measurable lesion and it is located in previously irradiated field, it must have demonstrated unequivocal progression according to RECIST, version 1.1.
    • If receiving radiation therapy, has a 2-week washout period following completion of the treatment prior to receiving the first study drug dose and continues to have at least 1 measureable lesion, per above criterion.
    • ECOG performance status of 0 or 1.
    • Has acceptable, applicable laboratory parameters.
    • Female subjects must not be pregnant.
    • If male, agrees to use an adequate method of contraception
    • Experienced resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia). If patient underwent major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
    • Willing to have fresh tumor samples collected during screening and at other time points designated as mandatory, per the Schedule of Study Assessments.
    • Able to understand and give written informed consent and comply with study procedures.
  • Patients meeting any of the following criteria are not eligible for study participation:

    • Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
    • Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
    • History of interstitial lung disease (ILD).
    • Allergy to benzamide or inactive components of entinostat.
    • History of allergies to any active or inactive ingredients of pembrolizumab.
    • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator, including, but not limited to:
      • Myocardial infarction or arterial thromboembolic events within 6 months prior to baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease, or a QTc interval > 470 msec.
      • Uncontrolled heart failure or hypertension, uncontrolled diabetes mellitus, or uncontrolled systemic infection.
      • Another known additional malignancy that is progressing or requires active treatment (excluding adequately treated basal cell carcinoma or cervical intraepithelial neoplasia [CIN]/cervical carcinoma in situ or melanoma in situ). Prior history of other cancer is allowed, as long as there is no active disease within the prior 5 years.
      • Evidence of pneumonitis or history of pneumonitis.
      • Active infection requiring systemic therapy.
      • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

    Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging [using the identical imaging modality for each assessment, either MRI or CT scan] for at least 4 weeks prior to the first dose of study drug and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 2 weeks prior to the first dose of study drug or are on stable or decreasing dose of ≤10 mg daily prednisone (or equivalent). This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.

    • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
    • Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
    • Received a live virus vaccination within 30 days of the first dose of treatment.
    • Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to baseline or who has not recovered (i.e., ≤Grade 1 or at baseline) from AEs due to agents administered more than 4 weeks earlier.
    • Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study baseline or who has not recovered (i.e., ≤Grade 1 or at baseline) from AEs due to a previously administered agent.

    Note: Patients with ≤Grade 2 neuropathy or ≤Grade 2 alopecia are an exception to this criterion and may qualify for the study.

    Note: If patient underwent major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

    • Received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte-colony stimulating factor [G-CSF], granulocyte macrophage-colony stimulating factor [GM-CSF], or recombinant erythropoietin) within 4 weeks prior to the first dose of study drug.
    • Currently receiving treatment with any other agent listed on the prohibited medication list such as valproic acid, or other systemic cancer agents within 14 days of the first dose of treatment.
    • If female, is pregnant, breastfeeding, or expecting to conceive, or if male, expect to father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug.
    • Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
    • Known active hepatitis B (e.g., hepatitis B surface antigen-reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid [qualitative]).
    • Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or sponsor staff directly involved with this study, unless prospective Institutional Review Board (IRB)/Ethics Committee (EC) approval (by chair or designee) is given allowing exception to this criterion for a specific patient.

BMS CA209-234

Pattern of Use and Safety/Effectiveness of Nivolumab in Routine Oncology Practice 

  • Physician & Study Coordinator
  • Synopsis
  • Inclusion Criteria
  • Exclusion Criteria
  • Study Coordinator

    Carolyn Seith, MSPH
    484-503-4702

    carolyn.seith@sluhn.org

     

  • Treatment Agent: N/A

    Synopsis:  The purpose of this study is to understand how nivolumab is used to treat patients who are diagnosed with advanced melanoma or lung cancer; and patients’ health-related experiences overall. Patients invited to participate are planning to start on nivolumab, either on its own or in combination with Ipilimumab as per routine care. The study will collect information about the patient’s health condition, how the patient is being treated with nivolumab and if there are any side effects from the treatment, and how the side effects are managed by the patient’s doctor. This study involves the collecting of information only and will not affect the treatment decision made by the patient’s physician. The data will be collected from the information previously recorded by the patient’s physician in the medical records, and future data that is collected by the patient’s doctor as part of routine care and treatment until the patient completes the study or withdraws consent. Participation in this study, the collected information and study results will help to understand how nivolumab is used and how best its side effects can be managed.

  • Individuals must meet all of the following inclusion criteria to be eligible for the study:

    • Age >= 18
    • Histologically or cytologically confirmed diagnosis of melanoma (including uveal
      melanoma) or lung cancer
    • Treatment with commercial nivolumab for the first time, alone or in combination with ipilimumab, for the approved indications of nivolumab within 14 days before informed consent for this study OR in the case where treatment has not yet been initiated, documentation that the treatment strategy is determined before an informed consent to study participation, and treatment is initiated within 28 days after informed consent.
  • Individuals will not be enrolled if 1 of the following exclusion criteria is met:

    • Prior participation in a clinical trial within the past 4 weeks.
    • Previously treated with anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies.
    • Previously treated with anti-CTLA-4 for lung cancer.
    • Current or pending participation in a clinical trial.
    • Current or pending systemic treatment for cancer other than melanoma and lung cancer.
    • Inability to comply with the study protocol.

Incyte INCB 39110-207

An Open-Label Phase 1/2 Study of INCB039110 in Combination With Osimertinib in Subjects With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

  • Physician & Study Coordinator
  • Synopsis
  • Inclusion Criteria
  • Exclusion Criteria
  • Study Coordinator

    Alyse LaLiberte, MPH

    484-503-4151

    Alyse.LaLiberte@sluhn.org
  • Treatment Agent: INCB039110; Osimertinib (AZD9291)

    Synopsis: You are being asked to participate in a clinical research study (“study”) to find out if INCB039110 when taken in combination with a drug called osimertinib (Tagrisso®) is safe and has beneficial effects in people who have Non-Small Cell Lung Cancer (NSCLC). You are being asked to take part in this study because you have NSCLC that is Stage IIIB or Stage IV.

    This is a research study and does not constitute treatment or therapy. INCB039110 is an investigational drug that is being studied by Incyte Corporation (the Sponsor of the research study) for use in combination with osimertinib. “Investigational” means that INCB039110 has not been approved by the US Food and Drug Administration (FDA) for use as a prescription or over-the-counter medication.

    • INCB039110 is a drug that blocks enzymes JAK kinase known as JAK1. “Kinases” are proteins inside cells that help cells live and grow.

    • INCB039110 has been given to over 590 patients to date. It has been given to healthy volunteers, patients with rheumatoid arthritis, psoriasis (a skin condition), and myelofibrosis (MF, a disease in which the bone marrow becomes replaced by scar tissue). INCB039110 has also been tested in combination with another targeted drug (INCB040093, a PI3K-delta inhibitor) in blood cancers and in solid tumors in combination with the chemotherapies gemcitabine and nab-paclitaxel. It is also currently being studied in combination with other targeted drugs and immunotherapy.

    • Osimertinib is being developed by AstraZeneca Pharmaceutical, LP and has been approved by the FDA for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, who have progressed on or after EGFR TKI therapy, under the name Tagrisso®, but osimertinib is considered an investigational drug in combination with INCB039110 for the treatment of NSCLC.

    • The purpose of this research study is to assess how safe and well tolerated the study drug INCB039110 is in combination with osimertinib in patients who have NSCLC. This study will also assess the ways in which these drugs are broken down in the body and eliminated, as well as looking at the effects that the drugs may have on your disease.

    • This is an open-label research study, which means that both the researchers and participants know which treatment is being administered. This research study has 2 Phases (parts): The main purpose of Phase 1 of the study is to determine a dose of INCB039110 that is safe and tolerable in combination with osimertinib. There are 2 groups (“cohorts”) in Phase 1, but all cohorts do not need to be completed before moving to Phase 2. There is a chance that the study will not move to Phase 2. The main purpose of Phase 2 is to see if the dose chosen in Phase 1 is effective in participants with a specific subtype of NSCLC (EGFR T790M mutation-positive).

    • The study doctor will tell you whether you will be in Phase 1 or Phase 2 of the study, and which cohort you might be in if you are in Phase 1.
    Together, throughout this informed consent, both INCB039110 and osimertinib may be collectively referred to as “study drug” or “study drugs”.

    Phase 1-Dose Escalation

    In Phase 1 of this study, a small group of subjects will be given a certain dose of INCB039110 in combination with a standard dose of osimertinib. This group will be evaluated before giving a higher dose of INCB039110 to the next group. In this study, approximately 9 subjects will receive:

    • 200 mg of INCB039110 once per day and 80 mg of osimertinib once per day

    If fewer than 3 subjects have a dose-limiting toxicity (DLT, which is a side effect that limits your ability to stay on study treatment) in the first 28 days, then approximately 9 additional subjects will receive 300 mg of INCB039110 and 80 mg of osimertinib daily. If 3 or more subjects have a DLT at the 200mg dose of INCB039110 then the study will be terminated and will not move into Phase 2. If fewer than 3 subjects have a DLT at the 300 mg dose, then the study will move into Phase 2 at the 300 mg dose; if 3 or more subjects have a DLT, then the study will move into Phase 2 at the 200 mg dose.

    Subjects will be enrolled in the Phase 1 portion of the study until approximately 18 subjects have been treated for 28 days.

    Phase 2

    The main purpose of Phase 2 is to evaluate the dose selected in Phase 1 in subjects who have a particular gene (EGFR T790M mutation-positive).

    A new set of approximately 30 subjects will receive:

    • 200 or 300 mg of INCB039110 once per day (depending on the dose determined in Phase 1).

    • 80 mg of osimertinib once per day

    The Phase 2 portion of the study will examine the dose of INCB039110 in combination with osimertinib that is identified in Phase 1. Approximately 30 patients diagnosed with EGFR T790M-mutant NSCLC will be enrolled in the Phase 2 portion of the study
    Your participation in either Phase 1 or 2 of the study will last for as long as your doctor feels you are benefitting from study treatment and are not having any severe side effects. You may decide to stop participating at any time. 
     
     

  • Key Inclusion Criteria:
    • Men and women, 18 years of age or older at screening.
    • Histologically or cytologically confirmed unresectable locally advanced (Stage IIIB) or metastatic (Stage IV) NSCLC.
    • Documented evidence of somatic activating mutation in EGFR (eg, G719X, exon 19 deletion, L858R, L861Q) in a tumor tissue sample. If a tissue sample is not available, then EGFR mutation status may be determined from circulating tumor DNA obtained from a blood sample using a validated or approved test kit.
    -Phase 1: Subjects must have previously received and progressed on or after treatment with an EGFR TKI. Additional lines of systemic therapy including investigational agents for locally advanced or metastatic NSCLC are allowed.
    -Phase 2: Subjects must not have received more than 1 prior line of therapy for locally advanced or metastatic NSCLC. First-line treatment must include an EGFR TKI, and subjects must have documented disease progression during or following treatment. Subjects with disease that progressed more than 6 months after completion of neoadjuvant/ adjuvant chemotherapy or chemoradiation therapy are eligible if they received an EGFR TKI as first-line treatment for advanced NSCLC.
    Subjects must have evidence of a T790M mutation in tumor tissue or plasma obtained after disease progression during or after treatment with an EGFR-TKI. T790M mutation status from a local laboratory is acceptable; however, a tumor tissue sample or plasma sample suitable for centralized T790M mutation analysis must be available. If archival tumor tissue has not been collected after progression on an EGFR TKI or is otherwise not available, a fresh biopsy specimen or plasma sample will be required. A minimum of 25 slides (or a tissue block capable of providing this number of slides) must be available.
    • Radiographically measurable or evaluable disease per RECIST v1.1. Tumor lesions situated in previously irradiated areas are considered measurable only if there is unambiguous radiological progression after radiotherapy in such lesions.
    • ECOG performance status 0 or 1.
    • Life expectancy of at least 12 weeks from screening, according investigator assessment.
    • ≤ 2 weeks for chemotherapy or radiation therapy, 5 half-lives for targeted small molecule therapy, or investigational agents have elapsed from the completion of previous therapy regimen before the initiation of study therapy. Subjects must have recovered to ≤ Grade 1 or be at a new stable baseline from any related toxicities before study therapy (exception of alopecia or ≤ Grade 2 peripheral neuropathy). A 1-week washout for palliative radiation to non–central nervous system (CNS) disease is permitted with sponsor approval.
    • Willingness to avoid pregnancy or fathering children based on the following criteria:
    -Woman of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 50 years of age).
    -Woman of childbearing potential who has a negative serum pregnancy test at screening and who agrees to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subject and their understanding confirmed.
    -Man who agrees to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subject and their understanding confirmed.

  • Key Exclusion Criteria:
    • Known active CNS metastases. Subjects with CNS metastases who have completed a course of therapy would be eligible provided that they are clinically stable for at least 4 weeks before study entry, defined as follows:
    -No evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases.
    -Subjects who are receiving concomitant corticosteroids must be on a stable or decreasing dose for at least 4 weeks before first dose of study treatment and off anticonvulsants for at least 4 weeks before study entry.
    • Insufficient renal, hepatic, and bone marrow function, defined as follows:
    -ANC < 1.5 × 109/L.
    -Platelet count < 100 × 109/L.
    -Hemoglobin < 9 g/dL.
    -Total bilirubin > 1.5 × upper limit of normal (ULN) if no liver metastases or > 3 × ULN in the presence of liver metastases or presence of documented Gilbert syndrome (unconjugated hyperbilirubinemia).
    -Aspartate aminotransferase > 2.5 × ULN, or > 5 × ULN for subjects with known hepatic metastases.
    -Alanine aminotransferase > 2.5 × ULN, or > 5 × ULN for subjects with known hepatic metastases.
    -Alkaline phosphatase > 2.5 × ULN, or > 5 × ULN for subjects with known bone metastases and no hepatic parenchymal metastases.
    -Serum creatinine > 1.5 × ULN or creatinine clearance < 50 mL/min measured or calculated by Cockroft-Gault equation for subjects with serum creatinine > 1.5 × ULN.
    • Inability to swallow food, or significant gastrointestinal disorder that, in the opinion of the investigator, could interfere with absorption of the study drug.
    • Clinically significant abnormalities found on an ECG. Subjects with a mean resting corrected QT interval (QTcF) > 470 milliseconds obtained during screening are excluded, as are subjects with any risk factor or concomitant medication requirement that may increase the risk of QTc prolongation or arrhythmia events. Subjects with left bundle branch block are excluded.
    • Clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class II, III, or IV congestive heart failure, and ongoing arrhythmia requiring therapy.
    • Past history of ILD, drug induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
    • Known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibodies).
    • Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment.
    • Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of reactivation. Subject cannot be positive for HBV DNA, HCV RNA, hepatitis B surface antigen, or anti–hepatitis B core antibody.
    • Current or previous other malignancy within 2 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive malignancy.
    • Use of any potent cytochrome P450 3A4 inducers or inhibitors within 14 days or 5 half- lives (whichever is longer) before the first dose of study treatment.

    • Major surgery within 4 weeks of the first dose of the study drug.
    • Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or hormonal therapy).
    • Any previous use of JAK inhibitor, osimertinib, or other EGFR-directed therapy for T790M-mt NSCLC.
    • Currently breastfeeding.
    • Previous reaction to any component of or INCB039110 or osimertinib, or known hypersensitivity to either active substance or any of their excipients.
    • Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.

Roche-Genentech GO29527

A PHASE III, OPEN-LABEL, RANDOMIZED STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF MPDL3280A (ANTI−PD-L1 ANTIBODY) COMPARED WITH BEST SUPPORTIVE CARE FOLLOWING ADJUVANT CISPLATIN-BASED CHEMOTHERAPY IN PD-L1−SELECTED PATIENTS WITH COMPLETELY RESECTED STAGE IB−IIIA NON−SMALL CELL LUNG CANCER

  • Physician & Study Coordinator
  • Synopsis
  • Inclusion Criteria
  • Exclusion Criteria
  • Study Coordinator

     Alyse LaLiberte, MPH

    484-503-4151

      Alyse.LaLiberte@sluhn.org
  • Treatment Agent: Atezolizumab (MPDL3280A)

    Synopsis: The primary efficacy objective of the study is to evaluate the efficacy of 16 cycles of Atezolizumab (MPDL3280A) treatment compared with best supportive care as measured by disease-free survival (DFS) as assessed by the investigator

  • Inclusion Criteria for Enrollment Phase

    • Age >/= 18 years
    • Ability to comply with protocol
    • ECOG performance status of 0 or 1
    • Histological or cytological diagnosis of Stage IB (tumors >/= 4 cm) -IIIA (T2-3 N0, T1-3 N1, T1-3 N2) NSCLC (per the UICC/AJCC staging system, 7th edition; Detterbeck et al. 2010)
    • Patients must have had complete resection of NSCLC 6-12 weeks (> / = 42 days and < / = 84 days) prior to enrollment and must be adequately recovered from surgery
    • Complete mediastinal lymph node dissection (MLND) is required. If mediastinoscopy was not performed preoperatively, it is required that, at a minimum, mediastinal lymph node systematic sampling will have occurred. Systematic sampling is defined as removal of at least one representative lymph node at specified levels. MLND entails resection of all lymph nodes at those same levels. For a right thoracotomy, sampling or MLND is required at levels 4 and 7 and for a left thoracotomy, levels 5 and/or 6 and 7. If there is clear documentation in the operative report or in a separately submitted addendum by the surgeon of exploration of the required lymph node areas, the patient will be considered eligible if no lymph nodes are found in those areas. If patients have documented N2 disease in one level (per the UICC/AJCC staging system, 7th edition; Detterbeck et al. 2010), not all levels need to be sampled.
    • Eligibility to receive a cisplatin-based chemotherapy regimen
    • Adequate hematologic and end-organ function, defined by the following laboratory results obtained within 14 days prior to enrollment
    • Women who are not postmenopausal (>/= 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of cisplatin-based chemotherapy.

    Inclusion Criteria for Randomized Phase

    • Women who are not postmenopausal (>/= 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug or BSC
  • Exclusion Criteria for Enrollment Phase

    • Illness or condition that may interfere with a participant's capacity to understand, follow, and/or comply with study procedures
    • Pregnant and lactating women
    • Treatment with prior systemic chemotherapy: Chemotherapy for early stage of malignancy with curative intent, provided that the last dose received was more than 5 years prior to enrollment and low-dose chemotherapy for non-malignant conditions may be allowed upon approval by the Medical Monitor
    • Hormonal cancer therapy or radiation therapy as prior cancer treatment within 5 years before enrollment
    • Treatment with any other investigational agent with therapeutic intent within 28 days prior to enrollment
    • Participants with hearing impairment
    • Known sensitivity to any component of the chemotherapy regimen the participant will be assigned to, or to mannitol
    • Prior treatment with cluster of differentiation (CD) 137 (CD137) agonists or immune checkpoint blockade therapies, anti-programmed death-1 (PD-1), and anti programmed death ligand 1 (PD-L1) therapeutic antibodies
    • Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS greater than [>] 90 percent [%]) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)
    • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
    • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
    • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
    • Positive test for human immunodeficiency virus (HIV)
    • Participants with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C
    • Active tuberculosis
    • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within the previous 3 months, unstable arrhythmias, or unstable angina
    • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
    • Prior allogeneic bone marrow transplantation or solid organ transplant
    • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications
    • Known tumor PD-L1 expression status as determined by an immunohistochemistry (IHC) assay from other clinical studies (e.g., participants whose PD-L1 expression status was determined during screening for entry into a study with anti-PD-1 or anti-PD-L1 antibodies but were not eligible are excluded)

    Specific Exclusions for Pemetrexed Treatment

    • Patients with squamous cell histology

    Exclusion Criteria for Randomized Phase

    • Signs or symptoms of infection within 14 days prior to randomization (severe infection within 28 days prior to randomization), including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
    • Received therapeutic oral or intravenous (IV) antibiotics within 14 days prior to randomization
    • Major surgical procedure within 28 days prior to randomization or anticipation of need for a major surgical procedure during the course of the study
    • Administration of a live, attenuated vaccine within 28 days prior to randomization or anticipation that such a live attenuated vaccine will be required during the study
    • Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to randomization: Prior treatment with cancer vaccines is allowed
    • Treatment with systemic corticosteroids or other immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 14 days prior to randomization

Alliance 151216

Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)

  • Physician & Study Coordinator
  • Synopsis
  • Inclusion Criteria
  • Exclusion Criteria
  • Study Coordinator

    Kendra Campbell, MA
    484-526-7952

    Kendra.campbell@sluhn.org

  • Treatment Agent: N/A

    Synopsis: The purpose of this research study is to examine lung cancer patients’ surgically removed tumors for certain genetic changes, and to possibly refer these patients to a treatment study with drugs that may specifically target tumors that have these genetic changes.

    A genetic test will be done to learn if your tumor has any of these genetic changes. This test will look at the genetic material of the tumor cells. We are interested to see if your tumor tissue might have one of the following two genetic changes:

    • Genetic changes in ALK (this will be referred to as ALK )
    • Genetic changes in EGFR (this will be referred to as EGFR)

    ALK and EGFR are both proteins found on the surface of cells. If your tumor is found to have one of these genetic changes you may be invited to participate na trial that will look at drugs which may target tumors that have these specific genetic changes. If your tumor is not found to have the genetic changes in ALK or EGFR, your doctor will provide you with other options for your care and you will be followed for 5 years. A doctor or research staff will contact you every 6 months for 5 years to determine the status of your cancer and your overall health. This will help doctors better understand what happens to patients receiving the standard treatment for the disease.

    • Completely resected non-squamous NSCLC
    • Pathologically staged IB >= 4 cm or stage IIA-IIIA disease
    • Adequate formalin-fixed, paraffin-embedded (FFPE) tissue available for central EGFR and ALK genotyping for all patients, including those already identified to carry eligible EGFR or ALK alterations
    • Clinical stage IB (>= 4 cm), II or IIIA non-squamous non-small cell lung cancer (NSCLC)
    • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
    • No patients who have received neoadjuvant therapy (chemo- or radio-therapy)
    • No interstitial fibrosis or lung disease
    • No prior or concurrent malignancies within 5 years, except non-melanoma skin carcinoma or in situ carcinomas
    • No prior treatment with agents targeting EGFR mutation or ALK rearrangement
    • Non-lactating and no patients known to be pregnant
    • No patients with local genotyping showing wild-type EGFR and ALK
    • No patients with local genotyping showing a Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation
    • Completely resected non-squamous NSCLC
    • Pathologically staged IB >= 4 cm or stage IIA-IIIA disease
    • Adequate formalin-fixed, paraffin-embedded (FFPE) tissue available for central EGFR and ALK genotyping for all patients, including those already identified to carry eligible EGFR or ALK alterations

Alliance 081105

Randomized Study of Erlotinib or VS Observation  in Patients With Completely Resected Epidermal Growth Factor Receptor (EGFR) Mutant Non-small Cell Lung Cancer (NSCLC)

  • Physician & Study Coordinator
  • Synopsis
  • Inclusion Criteria
  • Exclusion Criteria
  • Study Coordinator

    Kendra Campbell, MA
    484-526-7952 

    Kendra.campbell@sluhn.org

  • Treatment Agent: Erlotinib

    Synopsis: The purpose of this study is to compare any good and bad effects patients may have when treated with the standard treatment against patients who are treated with the standard treatment plus erlotinib (an investigational drug). You are being asked to take part in this research study because you have early stage non-small cell lung cancer that was surgically removed and may have been treated with chemotherapy and/or radiation. The tumor removed has a mutation of a gene called EGFR (Epidermal Growth Factor Receptor). We are trying to find out if this mutation could help us make decisions about which type of treatment is best for people with your type of cancer. People not in a research study are usually not treated with anything after they finish their chemotherapy although some of them may receive radiation therapy.

    • Previously registered to A151216, with the result of lung cancer harboring an EGFR exon 19 deletion or L858R mutation; the testing must have been performed by one of the following criteria:
      • Patient registered to A151216 and the assessment performed centrally by the protocol specified laboratory
      • By a local Clinical Laboratory Improvement Amendments (CLIA) certified laboratory; the report must indicate the result as well as the CLIA number of the laboratory that performed the assay; these patients will also have been registered to A151216, but can be enrolled on A081105 regardless of the central lab results
        • Patients with known resistant mutations in the EGFR tyrosine-kinase (TK) domain (T790M) are not eligible
        • Patients that are both EGFR mutant and anaplastic lymphoma kinase (ALK) rearrangements will be registered to A081105
    • Completely resected stage IB (>= 4 cm), II or IIIA non-squamous NSCLC with negative margins
    • Complete recovery from surgery and standard post-operative therapy (if required). Patients must be completely recovered from surgery at the time of randomization; the minimum time requirement between date of surgery and randomization must be at least 28 days, the maximum time requirement between surgery and randomization must be 90 days if no adjuvant chemotherapy was administered, 240 days if adjuvant chemotherapy was administered, and 300 days if adjuvant chemotherapy and radiation therapy was administered.
    • No interstitial fibrosis or lung disease
    • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
    • No prior or concurrent malignancies within 5 years, except non-melanoma skin carcinoma and in situ carcinomas
    • Non-pregnant and non-lactating
    • Granulocytes >= 1,500/ul
    • Platelets >= 100,000/ul
    • Total bilirubin =< 1.5 x upper limit of normal (ULN)
    • Serum glutamic oxaloacetic transaminase (SGOT) =< 1.5 x ULN
    • Serum creatinine =< 1.5 x ULN

ECOG 4512

A Randomized Phase III Trial for Surgically Resected Early Stage Non-Small Cell Lung Cancer: Crizotinib versus Observation for Patients with Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein

  • Physician & Study Coordinator
  • Synopsis
  • Inclusion Criteria
  • Exclusion Criteria
  • Study Coordinator

    Kendra Campbell, MA
    484-526-7952 

    Kendra.campbell@sluhn.org

  • Treatment Agent: Crizotinib

    Synopsis: The purpose of this research study is to compare any good and bad effects of using the study drug, crizotinib (also known as XALKORI®), after completion of surgery and, in some cases, after chemotherapy and/or radiation therapy for ALK-positive non-small cell lung cancer. The addition of crizotinib may help prevent your cancer from returning, but it could also cause side effects. This research study will allow the researchers to know whether this different approach is better, the same, or worse than the usual approach. To be better, the study drug should improve how long you are able to live by 2 years and 9 months (33 months total) or more compared to the usual approach. The study drug, crizotinib, is already FDA-approved for use in ALK-positive locally advanced or metastatic (spread to other areas of the body) non-small lung cancer. The use of crizotinib in this study is investigational (not approved by the FDA) because crizotinib (or placebo) will be prescribed for earlier stage disease after the cancer has been surgically removed. A placebo is a capsule that looks like the study drug but contains no medication.

    • Patients must have undergone complete surgical resection of their stage IB (>= 4 cm), II, or IIIA NSCLC per American Joint Committee on Cancer (AJCC) 7th edition and have had negative margins; N3 disease is not allowed
    • Baseline chest computed tomography (CT) must be performed within 3 months (90 days) prior to randomization to ensure no evidence of disease; if clinically indicated additional imaging studies must be performed to rule out metastatic disease
    • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
    • Patients must be registered to the ALCHEMIST-SCREEN (ALLIANCE A151216) trial prior to randomization
    • Positive for translocation or inversion events involving the ALK gene locus (e.g. resulting in echinoderm microtubule associated protein like 4 [EML4]-ALK fusion) as determined by the Vysis Break Point fluorescence in situ hybridization (FISH) assay and defined by an increase in the distance between 5' and 3' ALK probes or the loss of the 5' probe; this must have been performed:
      • By a local Clinical Laboratory Improvement Amendments (CLIA) certified laboratory: Report must indicate the results as well as the CLIA number of the laboratory which performed the assay; tissue must be available for submission for central, retrospective confirmation of the ALK fusion status via ALCHEMIST-SCREEN (ALLIANCE A151216) OR
      • Patient registered to and the ALK fusion status performed centrally on the ALCHEMIST-SCREEN (ALLIANCE A151216)
    • Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood or urine pregnancy test within 72 hours prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
    • Women of childbearing potential and sexually active males must be strongly advised to practice abstinence or use an accepted and effective method of contraception
    • Patients must NOT have uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
    • No known interstitial fibrosis or interstitial lung disease
    • No prior treatment with crizotinib or another ALK inhibitor
    • No ongoing cardiac dysrhythmias of grade >= 2 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, uncontrolled atrial fibrillation (any grade), or corrected QT (QTc) interval > 470 msec
    • No use of medications, herbals, or foods that are known potent cytochrome P450, subfamily 3A, polypeptide 4 (CYP3A4) inhibitors or inducers, included but not limited to those outlined
    • Patients must be adequately recovered from surgery at the time of randomization
    • The minimum time requirement between date of surgery and randomization must be at least 4 weeks (28 days)
    • The maximum time requirement between surgery and randomization must be:
      • 3 months (90 days) if no adjuvant chemotherapy was administered
      • 6 months (180 days) if adjuvant chemotherapy was administered
      • 8 months (240 days) if adjuvant chemotherapy and radiation therapy were administered
    • Patients must have completed any prior chemotherapy or radiation therapy 2 or more weeks (6 or more weeks for mitomycin and nitrosoureas) prior to randomization and be adequately recovered at the time of randomization NOTE: Patients taking low dose methotrexate for non-malignant conditions and other cytotoxic agents for non-malignant conditions are allowed to continue treatment while on study
    • Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) =< 2.5 x upper limit of normal (ULN)
    • Total serum bilirubin =< 1.5 x ULN
    • Absolute neutrophil count (ANC) >= 1500/mm^3
    • Platelets >= 30,000/mm^3
    • Hemoglobin >= 8.0 g/dL
    • Serum creatinine =< 2 x ULN
    • Prior to randomization patients with any non-hematologic toxicity from surgery, chemotherapy, or radiation must have recovered to grade =< 1 with the exception of alopecia and the criteria outlined
    • Patients must not have any history of cancer within 2 years from randomization, with the exception of in-situ carcinoma of the cervix or completely resected non-melanoma skin cancer
    • Patients may not be receiving any other investigational agents while on study

ECOG-ACRIN 5142 

Adjuvant Nivolumab in Resected Lung Cancers (ANVIL)-A Randomized Phase III Study of Nivolumab After Surgical Resection and Adjuvant Chemotherapy in Non-Small Cell Lung Cancers 

  • Physician & Study Coordinator
  • Synopsis
  • Inclusion Criteria
  • Exclusion Criteria
  • Study Coordinator

    Kendra Campbell, MA
    484-526-7952

    Kendra.campbell@sluhn.org
  • Treatment Agent: Nivolumab

    Synopsis: The purpose of this study is to find if adding the study drug, nivolumab (also known as OPVIDO®), will limit lung cancer from growing back in patients with early stage non-small cell lung cancer. Nivolumab is a drug that may turn on the body’s immune system to attack any cancer cells that may remain after surgery. The addition of nivolumab may help prevent your cancer from returning, but it could also cause side effects. This research study will allow researchers to find out whether this different treatment is better, the same, or worse than the usual treatment for lung cancer. The study drug, nivolumab, is already FDA-approved for use in non-small cell lung cancer that has previously been treated with chemotherapy. The use of nivolumab in this study is investigational (not approved by the FDA) in your type of cancer.

  •  •  Patients must have undergone complete surgical resection of their stage IB (>= 4 cm), II or IIIA NSCLC according to the American Joint Committee on Cancer (AJCC) 7th edition and have had negative surgical margins

    •  Baseline chest computed tomography (CT) must be performed within 1 month (30 days) of randomization to ensure no evidence of disease; if clinically indicated, additional imaging studies must be performed to rule out metastatic disease

    •  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

    •  Patients must be registered to the ALCHEMIST-SCREEN (ALLIANCE A151216) trial prior to randomization

    •  Non-squamous tumors must be epidermal growth factor receptor (EGFR) and anaplastic lymphoma receptor tyrosine kinase (ALK) wild-type (results ascertained in centrally as part of ALCHEMIST-SCREEN protocol)

    •  Tumors must have PD-L1 status tested centrally as part of the ALCHEMIST-SCREEN protocol

    •  Women must not be pregnant or breast-feeding

    •  All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

    •  Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse during the treatment period and for 31 weeks after the last nivolumab infusion

    •  Patients must NOT have uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements

    •  No prior treatment with an immune checkpoint inhibitor (anti-programmed cell death [PD]-1, anti-PD-L1, anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA4] monoclonal antibody)

    •  Patients must have adequately recovered from surgery and chemotherapy at the time of randomization

               o Minimum time between date of surgery and randomization is 4 weeks

               o Maximum time allowed between surgery and randomization:

         - 10 months if adjuvant chemotherapy and radiation therapy was administered

         - 8 months if adjuvant chemotherapy was administered

         - 3 months if no chemotherapy is administered

    • Patients must have completed and recovered from any adjuvant chemotherapy 2 or more weeks prior to randomization (6 weeks for mitomycin and nitrosoureas; 4 weeks for post-operative radiation therapy)

    • Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) =< 2.5 x upper limit normal

    • Total bilirubin =< 1.5 x upper limit of normal (ULN) (except in subjects with Gilbert syndrome who must have a total bilirubin < 3.0 x ULN)

    • White blood cell (WBC) >= 2000/uL

    • Neutrophils >= 1000/uL

    • Platelets >= 100 x 10^3/uL

    • Hemoglobin >= 8 g/dL

    • Serum creatinine =< 2 x ULN

    • Prior to randomization patients with any non-hematologic toxicity from surgery, chemotherapy and radiation therapy must have recovered to grade =< 1 with the exception of alopecia, ototoxicity and neuropathy

    • Patients must not have any history of active malignancy within two years from randomization deemed by the investigator to pose a higher risk of recurrence than the lung cancer in question

    • Patients must not be receiving any other investigational anti-cancer agents while on study

    • Patients must not have known or suspected autoimmune disease; subjects with type I diabetes mellitus, hypothyroidism requiring hormone replacement, or skin disorders not requiring systemic treatment are permitted to enroll

    • Patients must not have a condition requiring systemic corticosteroids equivalent to > 10 mg prednisone per day or other immunosuppressive medications within 2 weeks of randomization

    • Patients must not have known interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity

    • Patients must not have a known history of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection that is untreated and/or with a detectable viral load

    • Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab